This study evaluated endothelial versus steroidogenic cell proliferation throughout the lifespan of the primate corpus luteum during the menstrual cycle and simulated early pregnancy (CG treatment). Corpora lutea collected from rhesus monkeys (Macaca mulatta; n=3/day) on days 3-4, 7, 10, 12, 14 and 17 (menses) of the luteal phase during spontaneous menstrual cycles and after 1, 3, 6 or 9 days of hCG treatment beginning on day 9 of the luteal phase, were snap frozen in mounting medium for immunocytochemical and histochemical evaluation. Labeling index (percent positive nuclei) for Ki67 antigen, a cell proliferation marker, was determined in conjunction with cell specific markers. Platelet/ endothelial cell adhesion molecule-1 (PECAM-1), von Willebrand factor and the Ulex europaeus agglutinin-1 (i.e., lectin) binding site were used to identify endothelial cells. 3 -hydroxysteroid dehydrogenase (3 -HSD) activity was used to identify steroidogenic cells. The cell proliferation index was greatest (44.5 q 1.9%) on day 3-4 of the luteal phase, remained high on days 7 and 10 (34.6 q 0.3, 27.1 q 3.4%), followed by a sharp decline on day 12 (9.6 q 2.3%) which was sustained through menses. After one day of hCG treatment, cell proliferation was less than that observed on the equivalent day of the luteal phase (day 10); but thereafter, it was similar on days 3, 6 and 9 of simulated early pregnancy to those in the late luteal phase of the menstrual cycle (i.e., day 12-menses). Dual-label immunocytochemistry indicated that >85% of cells staining positively for the Ki67 antigen, also co-stained for PECAM-1. No cells stained positive for both 3 -HSD activity and Ki67 antigen. Thus, cellular proliferation within the primate corpus luteum varied during the luteal lifespan in the menstrual cycle and endothelial cells comprised the vast majority of proliferative cells, while steroidogenically active cells were not proliferating. Further, the elevation in progesterone secretion and sustained luteal weight that occurred during CG exposure simulating early pregnancy was not associated with an increase or maintenance of cellular proliferation.